Cardiac toxicity in breast cancer patients treated with dual HER2 blockade: A meta-analysis of randomized evidence.

Abstract

624 Background: The dual antiHER2 blockade has been shown promising results in patients with HER2-positive breast cancer. Whether this treatment strategy jeopardizes the risk for cardiac adverse events is unclear. We conducted a meta-analysis of randomized trials to investigate the risk of cardiac adverse events when a combination of anti-HER2 therapies is used. Methods: We searched Medline, the Cochrane library, as long as the electronic abstract databases of the major international congresses’ proceedings to identify randomized trials that evaluated the administration of anti-HER2 monotherapy (lapatinib or trastuzumab or pertuzumab) versus anti-HER2 combination therapy with or without chemotherapy in breast cancer. Study outcomes were the congestive heart failure (CHF) grade >/= 3 and left ventricular ejection fraction (LVEF) decline < 50% or more than 10% from baseline. We calculated pooled odds ratios (ORs) and 95% Confidence Intervals (CI) with the Peto method. Results: Six trials were considered eligible. Overall incidence results for CHF in the combined antiHER2 therapy and the antiHER2 monotherapy were 0.88 % (95% CI: 0.47% - 1.64%) and 1.49 % (95% CI: 0.98% - 2.23%). The incidence of LVEF decline was 3.1 % (95% CI: 2.2% – 4.4%) and 2.9% (95% CI: 2.1% - 4.1%) respectively. The OR of CHF was 0.58 (95% CI: 0.26-1.27, p-value= 0.17) while the OR of LVEF decline was 0.88 (95% CI: 0.53-1.48, p-value= 0.64). In subgroup analyses, there were no significant differences in CHF or LVEF decline among different treatment settings or types of antiHER2 therapy. Conclusions: This meta-analysis offers substantial randomized evidence from trials with well-defined cardiac evaluations that a dual anti-HER2 therapeutic approach does not increase the risk for cardiac toxicity.